Between one per cent and four per cent of the nuclear DNA of modern humans outside Africa came from Neanderthals

It is an interest that began with the pyramids and mummies of ancient Egypt. But Svante Pääbo has made his name not in archaeology but by resurrecting ancient DNA.

Earlier this year, a team that he led published a draft genome of Neanderthals, our close cousins with whom we shared common ancestors within the last half-a-million years ago.

Uneasy coexistence

Although Neanderthals and modern humans coexisted, perhaps uneasily, for several thousand years, the former went extinct about 30,000 years back. Comparing our genome with that of the Neanderthals provides vital clues about what in the genetic make-up of modern humans is so uniquely different.

Prof. Pääbo, director of the Department of Evolutionary Genetics at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, was in Thiruvananthapuram recently for the conference of the Human Frontier Science Programme.

“I was very interested in archaeology and my mother took me to Egypt when I was 11 or 12 or so,” he told this correspondent. “That made me totally fascinated and I wanted to become an archaeologist, excavate pyramids and find mummies.”

“But I had a far too romantic an idea about Egyptology,” he recalled with a grin. To his dismay, the course at the Uppsala University in Sweden revolved around linguistics, not fieldwork. “So then I didn't know what to do with my life.”

He switched to studying medicine and then opted to do a doctorate in molecular genetics.

But he didn't forget Egypt and its mummies. “I knew, of course, that there were hundreds and thousands of mummies from Egypt in museums. No one seemed to have tried to isolate DNA from them. So then I started doing that.”

Unsure of approval

As he was supposed to be working on immune defences against viral infections for his thesis, he wasn't sure that his supervisor would approve of this new line of research. So the work on DNA from Egyptian mummies was carried out in secret.

He was successful and in 1985 published a single-author paper in Nature titled “Molecular cloning of Ancient Egyptian mummy DNA.”

DNA degrades rapidly to really short fragments in ancient remains, said Dr. Pääbo. The piece of DNA that he had cloned was a long piece. So in hindsight, that piece was probably a contaminant that had crept in.

DNA present

However, a stained microscope slide showed that DNA was indeed present in the cell nuclei of the sample from a mummy.

Seeing the Nature paper, Allan Wilson at the University of California at Berkeley, who had pioneered using changes in proteins and DNA as molecular clocks to understand evolutionary processes, was so impressed that he asked if he could do sabbatical in Dr. Pääbo's laboratory! After correcting that misunderstanding, “I was in a very good position to ask if I could do a post-doctoral with him instead.”

Subsequently, returning to Europe as a full professor in Germany, Dr. Pääbo began work on Neanderthals. The type specimen for Neanderthals was, after all, in Germany. But these ancient remains are very valuable. So DNA retrieval had to be first demonstrated with the remains of cave bears, which are often found in the same caves as Neanderthal bones. Only then, after much negotiation, was it possible to get Neanderthal samples in 1996.

A year later, a paper on the genome sequence of Neanderthal DNA found in its mitochondria, the tiny energy-producing machinery in cells that are passed along from mother to child, was published in the journal Cell. That showed no contribution from Neanderthals to the mitochondrial DNA of modern humans.

However, when the draft genome sequence of the Neanderthal nuclear DNA was published in the journal Science in May this year, it indicated that between one per cent and four per cent of the nuclear DNA of modern humans outside Africa came from Neanderthals.

The question of whether or not Neanderthals have contributed to the gene pool of modern humans has been a contentious issue in palaeontology. “It is fascinating now when we get the nuclear genome to see there is a little bit of contribution,” pointed out Dr. Pääbo.

55 per cent chance

The draft version had just 1.3- to 1.5-fold coverage of the Neanderthal genome. “So if you are interested in some particular position in the genome, there is just about 55 per cent chance that we have seen it.” This was good enough for the first overview, “but we don't have everything.” The aim now was to achieve 10- to 20-fold coverage of the genome. Then “we will have almost every position that exists as one copy” in the Neanderthal genome.

It will then be possible to list of how modern humans differ from our very closest relatives.

Many of those changes will be trivial. But among them will be important ones that define fully modern humans.

There will not be many such changes. “So in protein-coding genes for example, we estimate that less than 200 amino acids will have changed recently and become fixed [in modern humans],” he added. Other scientists can then study what those changes do functionally.

In March this year, Dr. Pääbo and his colleagues published a paper on the mitochondrial DNA sequence from an ancient human bone found in a cave in southern Siberia in 2008.

The DNA sequence showed that the bone came from a hitherto unknown type of ancient human that shared a common ancestor with Neanderthals and modern humans about one million years ago.

A draft sequence of the nuclear genome of this hominin had been produced and “we are in the process of analysing that,” said Dr. Pääbo.

Timing changes

It would be interesting to see how this ancient human was related to present day humans and to Neanderthals, he observed. It would also then be possible to time changes that occurred along the human lineage.

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